It is known that the blood contains, in its normal condition, plasminogen which is not active for the fibrinolysis, and the plasminogen can be converted into plasmin, which is capable of lysing fibrin, in the presence of a plasminogen-activating substance. Such the plasminogen-activating substance is useful as a therapeutic medicine for thrombosis. At present, the plasminogen-activating substance is prepared from the urine of humans and this substance is called Urokinase. However, it is difficult to produce Urokinase on an industrial scale.
In the year 1963, it was discovered by S. Oshiba and S. Hata that the biles of dogs and rabbits contained a substance which was different from known bile acid salts but capable of activating plasminogen. Thereafter, it was revealed by them that the plasminogen-activating substance prepared from the biles of dogs and rabbits is a non-dialysable protein which belongs to a pseudoglobulin or albumin group, and can be precipitated with a 50% ammonium sulfate-saturated aqueous solution. They named their plasminogen-activating substance bilokinase (BK) [cf. J. Physiol. Soc., Japan, 29, 116-129 (1967)].
However, it was also found that the plasminogen-activating substance prepared from the biles of dogs and rabbits is easily inactivated by being heated at a temperature of 60.degree. C. for 30 minutes and the plasminogen-activating activity thereof can be exhibited in a relatively narrow range of pH of from 4 to 9. Furthermore, it is difficult to collect the biles of dogs and rabbits in a large amount.
Under the above described circumstances, it is strongly desired to provide a new type of plasminogen-activating substance which can be easily prepared in a large amount, and exhibits an excellent plasminogen-activating activity in a wide range of pH and a high resistance to deterioration at an elevated temperature.